22-23895034-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002415.2(MIF):c.282-6C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,545,856 control chromosomes in the GnomAD database, including 24,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2463 hom., cov: 33)

Exomes 𝑓: 0.18 ( 22307 hom. )

Consequence

MIF
NM_002415.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0007365

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.27

Variant links:

Genes affected

MIF (HGNC:7097): (macrophage migration inhibitory factor) This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids. This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate an additional role in integrin signaling pathways. [provided by RefSeq, Jul 2008]

MIF links:

MIF-AS1 (HGNC:27669): (MIF antisense RNA 1)

MIF-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 22-23895034-C-G is Benign according to our data. Variant chr22-23895034-C-G is described in ClinVar as [Benign]. Clinvar id is 3060033.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIF	NM_002415.2 linkuse as main transcript	c.282-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000215754.8
MIF-AS1	NR_038911.1 linkuse as main transcript	n.868G>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
MIF	ENST00000215754.8 linkuse as main transcript	c.282-6C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002415.2	P1
MIF-AS1	ENST00000406213.1 linkuse as main transcript	n.868G>C	non_coding_transcript_exon_variant	3/3	1
MIF	ENST00000465752.1 linkuse as main transcript	n.396C>G	non_coding_transcript_exon_variant	2/2	1
MIF	ENST00000498385.1 linkuse as main transcript	n.248-6C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26601

AN:

152042

Hom.:

2458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.194

AC:

30212

AN:

155428

Hom.:

3222

AF XY:

0.192

AC XY:

15817

AN XY:

82308

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.189

GnomAD4 exome

AF:

0.176

AC:

245858

AN:

1393700

Hom.:

22307

Cov.:

AF XY:

0.177

AC XY:

121390

AN XY:

686648

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.175

AC:

26628

AN:

152156

Hom.:

2463

Cov.:

AF XY:

0.180

AC XY:

13400

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.134

Hom.:

493

Bravo

AF:

0.171

Asia WGS

AF:

0.217

AC:

755

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MIF-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

1.6

Dann

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00074

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over